LAUSR

Abstract Background: Avoidant/Restrictive Food Intake Disorder (ARFID) is a recent diagnosis incorporated into the DSM-5 to provide diagnostic specificity to individuals who may have avoidant/restrictive eating behavior unrelated to body image/weight concerns and display three core profiles: insufficient intake/low interest in feeding, fear of aversive consequences related to food intake (e.g., choking) and avoidance based on sensory characteristics of food. Various studies have shown a higher preponderance of male patients in ARFID compared to other eating disorder groups. To elucidate potential sex differences in the neurobiology of ARFID, we examined food motivation pathways by assessing levels of key appetite regulating hormones, anorexigenic peptide YY (PYY) and orexigenic ghrelin, and fMRI activation of relevant brain circuitry in females compared to males with ARFID. Based on prior fMRI studies in healthy controls, we hypothesized that in a fasted state, females (vs. males) would demonstrate greater blood-oxygen-level-dependent (BOLD) activation in response to high-calorie food (vs. non-food) images in the orbitofrontal cortex (OFC) and the right lateral prefrontal cortex (LPFC), while males (vs. females) would demonstrate greater activation in the right hippocampus. Methods: Seventy-five adolescents and young adults with ARFID and sub-threshold ARFID (43 female) were studied after a 10-hour overnight fast. PYY and ghrelin levels were assessed in a subset of 62 individuals (31 female). All participants completed fMRI imaging in a 3T scanner while viewing images of foods, non-food items, and fixation stimuli. Functional MRI data were analyzed using SPM12. A priori regions of interest included the right lateral prefrontal cortex (LPFC), right hippocampus and orbitofrontal cortex (OFC). Secondary exploratory whole-brain analysis was also performed. Statistical significance is reported at the p<0.05 level. Results: Females and males did not differ in age ((mean±SD): 16.1±3.7 years) or BMI (19.9±5.4 kg/m2). There were no statistically significant differences between females and males in PYY (p=0.10) or ghrelin (p=0.47) levels. Furthermore, analysis of fMRI data yielded no significant differences between females and males with ARFID in a priori regions of interest (OFC: p(FWE-corr)>0.50; R LPFC: no suprathreshold clusters, or R hippocampus: p(FWE-corr)=0.25 and 0.33) or in the secondary whole-brain analysis (cluster p(FWE-corr)=0.304). Conclusion: This is the first study to investigate sex differences in the neurobiology of ARFID, an important line of research to advance treatment approaches. We found no sex-specific neurobiological differences in adolescents and young adults with ARFID. Future studies with larger sample sizes are needed to further investigate potential sex differences across the different ARFID profiles.